tbuckley/cabot-search huggingface dataset:
Yatagarasu: A single-arm, open-label, phase 2 study of apalutamide (APA) plus goserelin (GOS) for patients (pts) with far locally advanced or recurrent/metastatic (fLA/RM) and androgen receptor (AR)-expressing salivary gland carcinoma (SGC).
Authors: Yoshitaka Honma, Nobuya Monden, Keisuke Yamazaki, Satoshi Kano, Hironaga Satake, Shigenori Kadowaki, Toshitaka Nagao, Tomohiko Nakatogawa, Koji Fujii, Yosuke Koroki, Junya Aoyama, Shohei Ouchi, Tetsuro Ogawa, Sharon McCarthy, Sabine D. Brookman-May, Suneel Mundle, Jinhui Li, Yuichiro Tada
Journal: Journal of Clinical Oncology (2022)

6079 Background: Overexpression of AR is identified as a potential molecular target of SGC treatment. Combined androgen blockade (CAB) with bicalutamide has been evaluated previously, but the clinical usefulness of CAB with a next generation AR inhibitor has been unclear in SGC. We prospectively assessed the efficacy and safety of APA+GOS for pts with AR-expressing SGC. Methods: Eligible pts had fLA/RM SGC, and AR expression with at least 1% of cell nuclei immunohistochemistry staining positive. Pts were treated with APA 240 mg orally once daily and GOS 3.6 mg subcutaneously once 28 days. Primary endpoint was overall response rate (ORR) by central review according to RECIST v1.1, and a response (complete response [CR] or partial response [PR]) was confirmed by repeat assessments at least 4 weeks after the initial evaluation showing a response. Primary analysis was performed based on first 24 response evaluable (RE) pts who had been observed at least 24 weeks (Primary RE pts). The ORR was tested using exact test based on the binominal distribution, the null hypothesis for ORR of 14% was rejected when at least 8 of the 24 Primary RE pts were responders, and the efficacy was to be declared. Key secondary endpoints included clinical benefit rate (CBR), disease control rate (DCR), duration of response (DOR), and time to response (TTR) in the Primary RE pts, and overall survival (OS), progression free survival (PFS), and safety in the treated pts. Results: Twenty-six of the 31 pts treated with APA+GOS were regarded as RE by central review. For the 24 Primary RE pts, ORR was 25.0% (6/24), while 37.5% (9/24) including unconfirmed PR. Clinical benefit rate and DCR in the Primary RE pts were 50.0% and 70.8%, respectively. At the data cut-off (Apr 28, 2021), 5 of 6 pts with confirmed response were still on protocol treatment. Median PFS and OS in the treated pts were 7.43 months (mos) and not reached, respectively, with the median follow-up period of 8.57 mos. Grade 3 or higher treatment-related adverse events were reported in 4/31 (12.9%) pts, and the events were rash maculo-papular (n=2), anemia (n=1), and leukopenia (n=1). Conclusions: This is the first prospective trial evaluating CAB with APA for AR-expressing SGC. Although this study did not meet the predefined criteria of efficacy, clinically meaningful activity with well-tolerated safety profile of APA+GOS was shown. Clinical trial information: NCT04325828. [Table: see text]
Impact of intensive multimodal treatment on the outcomes of patients with anaplastic thyroid cancer.
Authors: Firas Baidoun, Omar Abdel-Rahman
Journal: Journal of Clinical Oncology (2022)

6082 Background: Anaplastic thyroid cancer (ATC) is a rare and aggressive type of thyroid malignancy with very poor prognosis and outcome despite therapy. The rarity of this disease and the poor functional status of ATC patients limit the ability to conduct clinical trials, thus there is a lack of large, controlled trials to guide treatment and evaluate the benefit of combined modality therapy. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with ATC at age 18 or older between 2004 and 2018. After excluding patients with unknown number of treatment modalities, Charlson-Deyo score of 3 or more and patients lost follow-up, we split the cohort into three groups according to the number of treatment modalities they received. Treatment modalities include surgery, radiation, and systemic therapy. Then, we evaluated the overall survival (OS) between the three groups. We studied the OS using Kaplan-Meier estimates and multivariate cox regression analyses to evaluate factors associated with OS. Additionally, propensity score matching (accounting for age, gender, race, Charlson-Deyo score, and clinical M stage) was used for more robust results. Results: A total of 3,460 patients with ATC were included in the analysis, of which 1,472 (42.5%) either received one type of therapy or did not receive any therapy (group1), 1,092 (31.6%) received bimodal therapy (group 2), and 896 (25.9%) received trimodal therapy (group 3). We found that group 3 had better OS compared to group 1 and group 2 (median OS 9.1 months vs 1.7 months and 4.9 months, respectively with P &lt; 0.001 for all). Propensity score matching yielded 896 patients in each group. We found that group 3 had better OS compared to group 1 and group 2 (median OS 9.1 months vs 1.9 months and 5.2 months, respectively with P &lt; 0.001 for all). Same trend was found in subgroup analysis when we split the cohort according to the metastatic status; in M0 group (median OS was 10.4 months vs 1.9 months and 6.1 months, respectively with P &lt; 0.001 for all), in M1 group (median OS was 5.9 months vs 1.4 months and 3.7 months, respectively with P &lt; 0.001 for all). On multivariate analysis, group 1 and group 2 were associated with worse OS compared to trimodal treatment (HR 2.721; 95% CI: 2.466 - 3.002 and HR 1.434; 95% CI: 1.299 - 1.582, P &lt; 0.001 for all). Conclusions: Patients with ATC who were treated with intensive trimodal therapy had statistically significant improvement in OS compared to patients who received less intense therapy. This survival benefit was observed in both metastatic and non-metastatic groups. While we acknowledge the limitations of this retrospective analysis, our results showed the critical role of intensive therapy approach in this aggressive malignancy.
Circulating tumor DNA profiling and serial analysis in salivary gland carcinomas reveal unique mutational subsets and actionable alterations.
Authors: Jeffery Scott Russell, Kathleen Claire Kerrigan, Dong Yang
Journal: Journal of Clinical Oncology (2022)

6097 Background: Salivary gland carcinoma is a rare head and neck malignancy without any FDA approved treatment options. ctDNA profiling has been shown to be a valuable tool in identifying novel targets and expanding potential therapeutic options. Here, we report the landscape of ctDNA in a large dataset of salivary gland carcinomas. Methods: Analysis of genomic results from blood samples with a diagnosis of salivary gland carcinoma that were prospectively collected between January 2017 to December 2021 for clinical Guardant360 testing. Histologic subtype was documented by ordering providers as available. Serial tests were defined as having Guardant360 analysis performed on more than one sample collected at more than one timepoint. Results: Among 222 patients tested with Guardant360, 59.5% were male and the median age was 64 years (range 22-93 years). Of reported diagnoses, 137 (61.7%) patients had salivary gland carcinoma NOS. The remaining samples were designated by specific salivary histology: 13 (5.9%) salivary gland mucoepidermoid carcinoma (SGMC), 19 (8.6%) salivary gland adenocarcinoma (SGA), 37 (16.7%) salivary gland adenoid cystic carcinoma (SGACC), and 16 (72%) salivary duct carcinoma (SDC). ctDNA genomic alterations (GAs) were identified in 205 (81.3%) of 252 samples. The median variant allele fraction was 0.6% (range 0.01%-46.4%). TMB was evaluated in 45 samples of which 33 were evaluable and the median and 80th percentile of TMB was 8.44 and 11.81 mut/Mb. MSI-H was not detected in any of the 181 samples tested for MSI. The most commonly altered genes were TP53, PIK3CA, ERBB2, ATM, EGFR and HRAS across all collected salivary samples. Further analysis stratified genetic alterations by tissue subtype. Other than TP53, common mutations by salivary gland carcinoma subtype included: PI3KCA (SGACC/SDC), ERBB2 (SGA), and EGFR (SGMC). In regards to serial analysis, 16 patients had at least 2 serial tests. When comparing the subsequent testing within the same patient, 3 patients had potentially new actionable GAs (including BRAF, KRAS mutations and EGFR amplification) on the subsequent test that were not identified on the original test. Conclusions: Blood-based liquid biopsy can be applied in salivary gland tumors to detect genomic alterations in ctDNA which may provide opportunities for therapeutic intervention in a cancer with limited treatment options. Additionally, ctDNA testing may be used to identify resistant alterations to potential therapy. Finally, longitudinal assessment of ctDNA may shed light on tumor evolution and additional therapeutic targets may be found. Further assessment of serial ctDNA analysis and the potential impact on patient clinical outcomes needs to be elucidated.
Camrelizumab in combination with concurrent chemoradiotherapy as first-line treatment for nonoperative head and neck cancer: A comparative study.
Authors: Feng Liu, Wenxiao Huang, Hui Wang, Cuihong Jiang, Hailin Zhang, Xiangwei Wu, Haolei Tan, Jinyun Li, Pingqing Tan, Lili He, Shuai Xiao
Journal: Journal of Clinical Oncology (2022)

6063 Background: We hypothesized that concurrent chemoradiotherapy (CCRT) plus concurrent and adjuvant camrelizumab as first-line treatmentwas associated with improved survival compared with concurrent chemoradiotherapy alone for nonoperative locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The purpose of this comparative study was to compare the efficacy and toxicity of CCRT plus concurrent and adjuvant camrelizumab versus CCRT alone in nonoperative locoregionally advanced HNSCC. Methods: One hundred and eighty patients with nonoperative locoregionally advanced HNSCC (cancer of the oral cavity, oropharyngeal cancer, hypopharyngeal cancer and laryngeal cancer) received either CCRT plus concurrent and adjuvant camrelizumab (camrelizumab + CCRT group, n = 90) or CCRT alone (CCRT alone group, n = 90). Patients in both groups received curative cisplatin-based concurrent chemoradiotherapy. The radiation dose was 70 Gy (2.0 Gy/fraction). In camrelizumab + CCRT group, concurrent camrelizumab (200mg/day on days 1, 22, 43) was added to CCRT, followed by adjuvant camrelizumab (200mg, every 3 weeks for 6 months or until disease progression, unacceptable adverse events or withdrawal of consent). Results: Compared with CCRT alone, the addition of concurrent and adjuvant camrelizumab significantly improved complete response (CR) rates (92.2% vs. 80.0%; P = 0.018), 3-year disease free survival (DFS, 72.2% vs. 56.7%; P = 0.029), locoregional recurrence-free survival (LRRFS, 76.7% vs. 61.1%; P = 0.024), and overall survival (OS, 78.9% vs. 63.3%; P = 0.033). Reactive cutaneous capillary endothelial proliferation was higher in the camrelizumab + CCRT group (6.7% vs. 0.0%; P = 0.013). No statistically significant differences in other acute (mucositis, leukopenia, thrombocytopenia, anemia, etc.) and late toxic effects (mucosal necrosis, trismus, cranial nerve palsy, etc.) were observed between the two groups. The addition of camrelizumab (CCRT plus camrelizumab vs. CCRT alone) was a significant independent prognostic factor for 3-year DFS, LRRFS and OS (P = 0.038, P = 0.032, and P = 0.048, respectively). Conclusions: Concurrent chemoradiotherapy plus concurrent and adjuvant camrelizumab as first-line treatment is associated with a considerable survival benefit, with acceptable adverse events, as compared with concurrent chemoradiotherapy alone, among patients with nonoperative locoregionally advanced head and neck squamous cell carcinoma. Our ongoing prospective clinical trial (registered with chictr.org.cn, number ChiCTR2200056298) will further investigate the efficacy of camrelizumab in combination with chemoradiotherapy for HNSCC.
Self-care for head and neck cancer survivors with lymphedema and fibrosis: A pilot randomized clinical trial.
Authors: Jie Deng, Alexander Lin, Subhash Aryal, John Nicholas Lukens, Erin McMenamin, Ryan Quinn, Joy Cohn, Bryan Spinelli, Barbara A. Murphy
Journal: Journal of Clinical Oncology (2022)

6094 Background: Lymphedema and fibrosis (LEF) are debilitating late effects in head and neck cancer survivors (HNCS). Initial therapy is usually directed by therapists following which patients undertake a LEF self-care program (SCP). No evidence based LEF-SCP are available. We report on the feasibility and preliminary efficacy data of a multifaceted LEF-SCP. Methods: 59 HNCS with LEF were randomized to: Usual care (n = 20), usual care + LEF-SCP (n = 20), and usual care + LEF-SCP + routine follow-up with a lymphedema therapist (n = 19). Assessments were conducted at baseline, 3-, 6-, 9-, and 12-months. Outcome measures include feasibility and preliminary efficacy (LEF progression, symptom burden, and jaw range of motion [ROM]). Multivariate covariance pattern model analysis was used to test for difference between arms. Results: 1) Feasibility: LEF-SCP training sessions - 80% completion rate; 90% satisfaction with the LEF-SCP; self-care adherence was similar between arms; no adverse event. 2) Preliminary Efficacy: Compared to usual care, participants randomized to LEF-SCP (+/- follow-up) showed a decrease in LEF severity (p &lt; 0.05), reduction in symptom burden (p &lt; 0.05), without significant improvement in jaw ROM. No significant differences were noted between the patients +/- follow-up with a lymphedema therapist. There was a trend to improved self-efficacy in patients participating in the LEF-SCP. Conclusions: The LEF-SCP is feasible and potentially efficacious for HNCS. Further testing is warranted. Clinical trial information: NCT03030859.
Cabozantinib (C) versus placebo (P) in patients (pts) with radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) who have progressed after prior VEGFR-targeted therapy: Outcomes in prespecified subgroups based on prior VEGFR-targeted therapy.
Authors: Jorge Hernando, Jaume Capdevila, Bruce Robinson, Steven I. Sherman, Barbara Jarząb, Chia-Chi Lin, Fernanda Vaisman, Ana Hoff, Erika Hitre, Daniel W. Bowles, Suvajit Sen, Jennifer Wright Oliver, Bhumsuk Keam, Marcia S. Brose
Journal: Journal of Clinical Oncology (2022)

6083 Background: Based on the results of the phase 3 COSMIC-311 trial, the multikinase inhibitor C was recently approved by the FDA for the treatment of RAIR DTC pts who progress after prior VEGFR-targeted therapies, such as lenvatinib (L) or sorafenib (S), and for whom there was no standard of care (Brose et al. Lancet Oncol. 2021). In an extended follow-up of the intent-to-treat (ITT) population, C-treated pts achieved a median (m) progression-free survival (PFS) of 11 months (mo) vs 1.9 mo with P (HR 0.22, 96% CI 0.15–0.32, P &lt;.0001); here we present outcomes for prespecified subgroups who received prior L, S, or both. Methods: Pts were randomized 2:1 to C (60 mg QD) or P. P pts could cross over to open-label C upon disease progression per confirmation by blinded independent radiology committee (BIRC). The primary endpoints were PFS (ITT) and objective response rate (first 100 randomized pts), per RECIST v1.1 by BIRC. Pts must have received L or S and progressed during or after 1–2 prior VEGFR inhibitors. Results: After a median follow-up of 10.1 mo, 258 pts (170 C, 88 P) had been randomized (data cutoff 8 Feb 2021); 96 (̃37%) had received prior S (no L), 102 (̃40%) prior L (no S), and 60 (̃23%) prior S and L. Median PFS was 16.6 for C vs 3.2 mo for P in prior S (no L) (HR 0.13, 95% CI 0.06–0.26); 5.8 vs 1.9 mo in prior L (no S) (HR 0.28, 95% CI 0.16–0.48), and 7.6 vs 1.9 mo in prior S and L (HR 0.27, 95% CI 0.13–0.54). In the C arm, 21% of pts in prior S (no L), 3% in prior L (no S), and 8% in S and L subgroups had confirmed partial response, and 1 pt had a confirmed complete response in prior L (no S); there were no responses with P. Stable disease as best response was 67% for C vs 45% for P in prior S (no L), 68% vs 32% in prior L (no S), and 74% vs 38% in prior S and L. Median duration of C-exposure was 7.0 mo in prior S (no L), 5.6 mo in prior L (no S) and 5.9 mo in prior S and L. Grade 3/4 treatment-emergent adverse events (TEAE) occurred in 63% pts in prior S (no L), 57% in prior L (no S), and 69% in prior S and L. Discontinuations of C due to TEAE occurred in 16% of pts in prior S (no L), 13% in prior L (no S), and 23% in prior S and L. There were no treatment-related deaths. Conclusions: In the extended follow-up, C maintained its superior PFS vs P irrespective of prior L and/or S. AEs in each subgroup were consistent with that of the overall population. This is also the first phase 3 study demonstrating a clinical benefit with C after prior L in RAIR DTC pts. Clinical trial information: NCT03690388.
Phase I study of AIC100 in relapsed and/or refractory advanced thyroid cancer and anaplastic thyroid cancer.
Authors: Jing Mei Hsu, Eric von Hofe, Yen-Michael Hsu, Jae-Hung Shieh, Ok-Kyong Chaekal, Danielle Guarneri, Thomas J. Fahey, Jana Ivanidze, Janusz Puc, Karrie Du, Ashlee You, Theresa Scognamiglio, Ljiljana Vasovic, Melissa Cushing, Moonsoo Jin, Koen Van Besien
Journal: Journal of Clinical Oncology (2022)

6093 Background: ICAM-1 is a cell surface glycoprotein that is typically expressed on endothelial cells and immune cells and a ligand for LFA-1 integrin. It is also overexpressed in several malignancies, in particular anaplastic and advanced thyroid cancer. We designed an affinity tuned ICAM-1-directed CAR T cell (micromolar affinity) that preferentially binds overexpressed ICAM-1 on tumor cells and spares normal cells. The CAR T cells also express somatostatin receptor 2 (SSTR2), which allows tracking of CAR T cells in vivo via DOTATATE PET/CT scan. Murine studies showed excellent responses in ICAM-1 expressing thyroid cancer without significant toxicities. We are conducting a first-in-human phase 1 clinical trial to evaluate the feasibility, safety and preliminary efficacy of ICAM-1 in patients with relapsed/refractory thyroid cancer or anaplastic thyroid cancer who are BRAF wild-type, or BRAF mutated after failure of BRAF specific therapy (NCT04420754). Methods: This is a dose-escalation study with modified toxicity probability interval design and cohorts of 3 Patients. Patients receive a single dose of 1x 10 7 (Cohort 1), 1 x 10 8 (Cohort 2) or 5 x 10 8 (Cohort 3) ICAM-1 CAR T cells after FLU/CY lymphodepleting (LD) chemotherapy. Additional CAR T infusion is allowed if patients achieve partial response or stable disease. Whole-body Fluorodeoxyglucose (FDG) and DOTATATE PET/CT is used to stage tumor and track CAR T cells in vivo, respectively. Results: All ICAM-1 CAR T infusion products met target transduction efficiency. Two patients with progressive anaplastic thyroid cancer received ICAM-1 CAR T therapy at dose-level I. Evaluation of CAR T cellular kinetics demonstrated transient peripheral blood CAR T cell expansion. One patient developed grade 1 cytokine release syndrome (CRS) with fever. Several tumor lesions from this patient showed DOTATATE avidity, indicating CAR T homing to the tumor, concomitant with decrease in FDG avidity, suggesting biological activity at ̃2 weeks post CAR T infusion. DOTATATE avidity at 2 weeks post CAR T infusion also appeared to match that of CAR T abundance in the blood. Updated results on additional patients and cohorts will be presented. Conclusions: Adoptive cellular therapy with ICAM-1 directed CAR T is safe and feasible at dose level 1 in patients with anaplastic thyroid cancer. DOTATATE PET allows visualization of expansion and homing of SSTR2 expressing CAR T cells, while concomitant FDG PET permits correlation with biological activity. Clinical trial information: NCT04420754.
The effect of anlotinib on unresectable differentiated thyroid cancer (T4): A retrospective study.
Authors: Xin Wu, Han Luo, Xingchen Peng, Peiheng Li, Xiangyu Kong, Qiaoyue Tan, Jun Liu, Rui Huang, Zhihui Li
Journal: Journal of Clinical Oncology (2022)

6096 Background: Though the majority of differentiated thyroid cancer (DTC) patients obtained a good prognosis after standardized therapy, approximately 15% of DTC patients will progress to unresectable disease. Part of locally advanced (T4) thyroid cancer patients with progressive invasion into vasculature/windpipe/esophagus lost the surgery opportunity because of difficult in achieving R0/R1 resection. The study aimed to evaluate the efficacy and safety of anlotinib in T4 PTC. Methods: Retrospectively included T4 papillary thyroid cancer (PTC) patients from West China Hospital of Sichuan University between Sep. 2020 and Feb. 2022. The patients were prescribed with Anlotinib (12 mg orally daily, two weeks on/one week off) at least two courses. The tumor response was defined by RECIST v. 1.1. The primary endpoint was objective response rate (ORR). Results: The study included 22 T4 PTC patients, including 8 patients with lung metastasis. The median age of patients was 59.2 years, 8/22 patients were male. The median follow-up was 5.5 months (2-13 months). Totally, the ORR was 68.2% (CR: 9.1%; PR: 59.1%), disease control rate (DCR) was 95.5% (SD: 27.3%), one patient progressed (PD). 8 patients with lung metastasis, the ORR was 75% (6/8). The average tumor shrinkage rate was 42.1%. And two female patients (T4aN1M1 and T4bN1M0 respectively) obtained CR. Additionally, one juvenile patient (14 y) also response to Anlotinib treatment with 55.2% tumor shrinkage, and no obvious AE was observed in this patient. Most adverse events (AEs) were grade 1 or 2. Common AEs of all grades were hypertension (68.2%), hypertriglyceridemia (36.4%), proteinuria (31.8%), and tended to discontinue when treatment ceased. Conclusions: Anlotinib demonstrated antitumor activity in the treatment of unresectable T4 PTC; Juvenile PTC patients also response to Anlotinib treatment; Anlotinib treatment was tolerable in T4 PTC patients.